Genetic Research: Positive Results Towards Hearing Loss Treatment

Monday, September 10th, 2007

It is probably a fair statement that millions of people around the world who suffer from hearing loss wish that modern medicine could restore their hearing. The good news is that a cure is now within the realm of possibility.

At least two recent hearing research studies focusing on hearing restoration through gene therapy came up with positive and promising results that bring us a step closer to finding the elusive cure for genetic or acquired hearing loss, which affects an estimated 500 million people worldwide, including more than 30 million Americans.

Belgian scientists have identified a gene, TGBF1, responsible for the most common cause of hearing loss among white adults -- otosclerosis. It causes progressive hearing impairment as the build up of growing bone in the middle ear interrupts sound waves passing to the inner ear. Currently treatment of otosclerosis relies on two primary options: hearing aids and a surgery called a stapedectomy. Hearing aids are usually very effective early in the course of the disease, but eventually a stapedectomy may be required for definitive treatment. Researchers, who presented their findings in June 2007 at the annual meeting of the European Society of Human Genetics in Nice, France, hope the new data will pave the way to better forms of treatment in the future.

Sometimes Its in the Hair

Unlike otosclerosis, which is hereditary, many cases of hearing impairment are caused by the loss of hair not the ones on the head, but the tiny sensory receptors located in the cochlea of the inner ear, which detect and transmit sound to the brain. Age, exposure to noise or damage from certain medications can cause these hair cells to die off, resulting in a hearing disability. Now there may be a way to save these crucial hair cells and, subsequently, restore the hearing.

University of Virginia Health System Associate Professor Dr. Jeffrey Holt and his colleagues targeted a gene known as KCNQ4, which causes genetic hearing loss when mutated. They engineered a correct form of the gene and created a gene therapy delivery system that successfully transferred the KCNQ4 into human hair cells harvested from the inner ear.

This proof-of-principle experiment showed that the system we developed works, and that KCNQ4 gene therapy might be an effective strategy to cure deafness in patients who carry mutations of that gene, Dr. Holt says.

The Genes May Hold the Answer

In fact, Dr. Holt is not the first researcher to have discovered the miraculous healing powers of gene therapy.

In 1988, when genetics were still a relatively new field, James Watson, one of the most influential genetics researchers and a co-discoverer of the structure of DNA said: "We used to think that our fate was in our stars, but now we know that, in large measure, our fate is in our genes."

What exactly is gene therapy and how does it make us healthy? If there is a simple way to explain this highly complex science it is three-fold: it consists of introducing a new gene into the body to help fight a specific disease; inactivating, or knocking out, a mutated gene that is not functioning properly; replacing a mutated gene that causes disease with a healthy copy of that gene, as in the case of Dr. Holts research.

Current uses of gene therapy focus on treating or curing a slew of existing conditions. In recent studies U.S. scientists discovered that gene therapy might be effective in restoring sight in some people, reverse heart failure, increase the movement control of Parkinsons disease patients, and even suppress a gene that is crucial to HIV infection.

In the future, as doctors will know more about which genes contribute to which diseases, the focus could shift to prevention. But, even though gene therapy may seem like a convenient and reliable cure-all for various ailments, it could also backfire.

How? Since gene therapy involves transferring healthy genes into the cells of a patient to replace or repair the ones causing the disease, the genetic material may be delivered attached to a virus to get past the bodys defenses. In at least one case several years ago, this procedure resulted in a death of an 18-year-old treated for a rare liver disorder. That is one of the reasons why some in the medical and scientific community advocate gene therapy only for patients who have no other treatment options.

What About the Ear? Stay Tuned!

Dr. Holt says about 70 genes that carry mutations causing deafness have so far been identified. Each of them will have to be tested to determine whether gene therapy can offer a potential cure for patients who carry those mutations.

Before any of these strategies can be tested in humans other important questions must be answered, Dr. Holt says. For example, do these strategies cause any toxic side effects elsewhere in the patient, since weve only examined the inner ear tissue so far? Can they produce a long-term cure? And, can they be developed in a cost-effective manner?

Although the trials are promising, applying the technique to real-life patients is not exactly around the corner, Dr. Holt says, citing budgetary constraints as one of main reasons for the lag. As the National Institutes of Health budget keeps going down, there is less and less money available, he says. If we had the money to do the work and to recruit more talented scientists, I would venture a guess that gene therapy strategies to treat inner ear disorders could be available within the next decade.

To paraphrase James Walton, we now know that better hearing may be in our genes, but, for the time being at least, the fate of gene therapy is up in the air.